A coding variant in SR-BI (I179N) significantly increases atherosclerosis in mice
| العنوان: | A coding variant in SR-BI (I179N) significantly increases atherosclerosis in mice |
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| المؤلفون: | John S. Millar, Anthony P Kent, Daniel J. Rader, Ioannis M. Stylianou, Geoffrey F.S. Lim, Antonino Picataggi |
| المصدر: | Mammalian Genome. 24:257-265 |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Biology, Mice, chemistry.chemical_compound, In vivo, Internal medicine, Genetics, medicine, Animals, Genetic Predisposition to Disease, Gene, Cholesterol, Cholesterol, HDL, Mutagenesis, Cholesterol, LDL, Plasma levels, Scavenger Receptors, Class B, Atherosclerosis, SCARB1, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, Liver, Receptors, LDL, chemistry, Splenomegaly, Immunology, LDL receptor, Female, lipids (amino acids, peptides, and proteins), Scavenger Receptor Class B Member 1 |
| الوصف: | Human coding variants in scavenger receptor class B member 1 (SR-BI; gene name SCARB1) have recently been identified as being associated with plasma levels of HDL cholesterol. However, a link between coding variants and atherosclerosis has not yet been established. In this study we set out to examine the impact of a SR-BI coding variant in vivo. A mouse model with a coding variant in SR-BI (I179N), identified through a mutagenesis screen, was crossed with Ldlr −/− mice, and these mice were maintained on a Western-type diet to promote atherosclerosis. Mice showed 56 and 125 % increased atherosclerosis in female and male Ldlr −/− Scarb1 I179N mice, respectively, when compared to gender-matched Ldlr −/− control mice. As expected, HDL cholesteryl ester uptake was impaired in Ldlr −/− Scarb1 I179N mice compared to Ldlr –/– control mice, with a net effect of increased small and very small LDL cholesterol in Ldlr −/− Scarb1 I179N mice being the most probable cause of the observed increased atherosclerosis. Our data show that non-null coding variants in SR-BI can have a large significant impact on atherosclerosis, even if plasma lipid levels are not dramatically affected, and that human mutations in other candidate lipid genes could significantly impact atherosclerosis. |
| تدمد: | 1432-1777 0938-8990 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f2941052af924febd8914572c7a84a85Test https://doi.org/10.1007/s00335-013-9459-xTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....f2941052af924febd8914572c7a84a85 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321777 09388990 |
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